Glial scar survives until the chronic phase by recruiting scar-forming astrocytes after spinal cord injury

被引：20

作者：

Tamaru, Tetsuya ^{[1
]}

Kobayakawa, Kazu ^{[1
]}

Saiwai, Hirokazu ^{[1
]}

Konno, Daijiro ^{[2
]}

Kijima, Ken ^{[1
]}

Yoshizaki, Shingo ^{[3
]}

Hata, Kazuhiro ^{[1
]}

Iura, Hirotaka ^{[1
]}

Ono, Gentaro ^{[1
]}

Haruta, Yohei ^{[1
]}

Kitade, Kazuki ^{[1
]}

Iida, Kei-Ichiro ^{[1
]}

Kawaguchi, Ken-Ichi ^{[1
]}

Matsumoto, Yoshihiro ^{[1
]}

Kubota, Kensuke ^{[4
]}

Maeda, Takeshi ^{[4
]}

Okada, Seiji ^{[5
]}

Nakashima, Yasuharu ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Orthoped Surg, Fukuoka, Japan

[2] Engn Kindai Univ, Fac Sci, Dept Energy & Mat, Higashiosaka, Japan

[3] Kyushu Univ Beppu Hosp, Dept Orthoped Surg, Oita, Japan

[4] Spinal Injuries Ctr, Dept Orthoped Surg, Iizuka, Japan

[5] Osaka Univ, Grad Sch Med Sci, Dept Orthoped Surg, Suita, Japan

来源：

EXPERIMENTAL NEUROLOGY | 2023年 / 359卷

关键词：

Spinal cord injury; Chronic phase; Glial scar; Reactive astrocyte; Scar-forming astrocyte; 1-integrin; REACTIVE ASTROCYTES; REGENERATION;

D O I：

10.1016/j.expneurol.2022.114264

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Spinal cord injury (SCI) causes reactive astrogliosis, the sequential phenotypic change of astrocytes in which naive astrocytes (NAs) transform into reactive astrocytes (RAs) and subsequently become scar-forming astrocytes (SAs), resulting in glial scar formation around the lesion site and thereby limiting axonal regeneration and motor/sensory functional recovery. Inhibiting the transformation of RAs into SAs in the acute phase attenuates the reactive astrogliosis and promotes regeneration. However, whether or not SAs once formed can revert to RAs or SAs is unclear. We performed selective isolation of astrocytes from glial scars at different time points for a gene expression analysis and found that the expression of Sox9, an important transcriptional factor for glial cell dif-ferentiation, was significantly increased in chronic phase astrocytes (CAs) compared to SAs in the sub-acute phase. Furthermore, CAs showed a significantly lower expression of chondroitin sulfate proteoglycan (CSPG)-related genes than SAs. These results indicated that SAs changed their phenotypes according to the surrounding environment of the injured spinal cord over time. Even though the integrin-N-cadherin pathway is critical for glial scar formation, collagen-I-grown scar-forming astrocytes (Col-I-SAs) did not change their phenotype after depleting the effect of integrin or N-cadherin. In addition, we found that Col-I-SAs transplanted into a naive spinal cord formed glial scar again by maintaining a high expression of genes involved in the integrin-N-cadherin pathway and a low expression of CSPG-related genes. Interestingly, the transplanted Col-I-SAs changed NAs into SAs, and anti-beta 1-integrin antibody blocked the recruitment of SAs while reducing the volume of glial scar in the chronic phase. Our findings indicate that while the characteristics of glial scars change over time after SCI, SAs have a cell-autonomous function to form and maintain a glial scar, highlighting the basic mechanism underlying the persistence of glial scars after central nervous system injury until the chronic phase, which may be a ther-apeutic target.

引用

页数：11

共 31 条

[11] Locomotor Training Increases Synaptic Structure With High NGL-2 Expression After Spinal Cord Hemisection [J].